Keto acetal compounds and their preparation



Patented Mar. 10, .1953

UNITED PATENT OFFICE" KETO ACETAL COMPOUNDS AND THEIR PREPARATION DavidI. Weisblat, \Galesburg, :and Barney Magerlein, Kalamazoo, Mich.,assignors ,to The Upjohn Company, Kalamazoo, Mich.,a eorporation ofMichigan No Drawing. Application Mar 18, .1952, Serial "No. 286322 15Claims. (Cl. 260470) This invention relates to certain keto acetalestersand acidsrand to a method for :their preparation. This applicationa -.,eontinuation- -in part .of-applicaLtion Serial No.63,45'3pfiledDecember x3,1948.

Keto cacetal-comp'ounds of the invention, which can be prepared by the:method ;,given herein, sometimes referred to herein has .N-.(3,-3-.dialkorgyJ-ketopnopyl) :N- rtarylsulfonyl) peaminobenzoatecompounds havestheggeneric formula media given, andinth'osegivensubsequentlynepresents zero :or the -;integer..1, i. e. thosec0nte1-nin-g either no giutamic acid or esticrrresidue --,o r only one-glutamic :acid or ester residue, and the method will he described withparticular reference thereto.

. "Compounds having 41118 generic fonmula given above :are of particular:evalue ask-intermediates the preparation of compounds similartotorcidentical with certain naturallyoccurr'mg compounds (aim-0),on-Q'o-mHHNGcotNnenomcmo 0 non 1 enzoate compound wherein R "is amember o'f.;the group consisting or hydrogen and the :alkyl radicals.and n .is a member dfthegroup consistingoi zero t.and"thepos'itivefintegers "1 to .Z, inclusive. They ,thusinelude N'substitution products of 'p-aminobenzoic acids, of,p-aminobenzoyleglutamic acid, of the .p-aminobenzoy1+g1utamylg1utamicacids having up to '7 glutanii'c :acid residues in the ,mc'ilecule,

and of their esters, theiNesubstituentlbeinglin In the structuralIformulae egiven herein :and in the appendedrilaims, aromatic.nucleisare represented by one 'ormore s'impl'e i'hexajgons. In the"naming go'f compounds "having the ,generic formula given and of othercompounds mentioned herein wherein both aglutamic acid residue :and ap-aimno'benzoic acid "residue .are included in the moleculejth'enitrogen atom .of theglutamic acid residue is, forconveniencelherein.referred to :by the 'symbol N "and the nitrogen vatom.of the .p-aminobenzoicacid.residueistreferredLtolby the symbol N.indicatedibythe,genericiormula, compounds used inorpreparedlby..the,pro.c-

ess of Tthe linvention which :.contain -more lthan one jglutamic acid.or tester residue vare. .those wherein only the jgamma carboxylyroupsQ-are involvedin theppeptidellinkages. TBreferredecompoundsusedlin ornprenaredlby the methodnf the invention are those Whereinrn'ofthergeneric 'for-r ofthe'iolicacid roup. 'Ihusas described in'iparent application ..referr.ed to, the Iketo acetall compounds '(IV) ofthe invention can "be condensed readily with 2,4,5etriaminoefi hydmxwpyrimidine to form alkyl "N-(IZ-amino-eihydroxy-fiepteridyl) emethyl)p-eaminobenzoates 0r dialkyl. :N'-.(N-;( (2eaminoeehydroxy epteridyl)methyl) N- '(arylsulfonyl) paminobenzoyl) glutamates, .91 the .freeacids, depending upo the particularlketo uacetal esterpr acid emiiloyed.These l latter ccompounds can, in turmihy'hydrdlysisof the ester groupswith 'alkalies in lthegqase m n s .t 'be described are, however,notrlimited asto Ithe econfigurationtof the te'lutamicacid liesiduesinvolved.

N- (arylsulfonyl)-p-aminobenzoate ester 4 subsequent reactions. Gentlealkaline hydrolysis of the N- (3,3-dialkoxy-2-ketopropyl) -N-(arylsulfonyD-p-aminobenzoate compounds which are esters leads to theformation of the corresponding acids. The hydrolysis can be effected bymixing the ester with an aqueous or alcoholic alkali. Upon acidifyingthe cold aqueous reaction mixture, the acid is precipitated in the formof a solid or oily material which is generally somewhat yellowish incolor. The solid compounds can be purified, if desired, byrecrystallization from alcohol.

Certain of the N-(arylsulfonyl)-p-aminobenzoate esters (II) aredescribed and claimed in co-pending application Serial-No. 41,888, filed1 oxidation (Ci-Oz)N-(3,3-dlalkoxy-2-ketopropyl)-N-Karylsullonyl)-p-aminobenzoate compoundThe process of the invention, as illustrated in the accompanyingreaction chart wherein the formulae of the compounds given are numberedto correspond with the following description and wherein n and B havethe values given previously, comprises the step of oxidizing an N-(3,3-dialkoxy-2-hydroxypropyl) -N-(arylsulfonyl) paminobenzoate compound(III) to form an N- (3,3-dialkoxy-2-ketopropyl) N (arylsulfonyl)p-aminobenzoate compound (IV). The oxidation can be carried outconveniently using chromic oxide, although any other suitable oxidizingagent can be employed. Either the hydroxy acetal acids or their alkylesters can be oxidized to the corresponding keto acetal acids or esters.Both the hydroxy acetal esters and the keto acetal esters can behydrolyzed readily to the corresponding hydroxy acetal acids and ketoacetal acids.

The oxidation of an N-(3,3-dialkoxy-2-hydroxypropyl) -N-(arylsulfonyl)-p-aminobenzoate compound to an N-(3,3-dialkoxy-Z-ketopropyl)-N-(arylsulfonic) -p-aminobenzoate compound can becarriedout convenientlyby dissolving the hydroxy compound and chromic anhydride in glacialacetic acid and agitating the mixture for several hours, 'e. g. at roomtemperature. The reaction mixture then generally consists of a mixtureof liquid and solid substances from which the keto compound can berecovered in any convenient manner. If desired, the mixture can beagitated thoroughly with ether and filtered or it can be diluted withwater andthen extracted with benzene or ethyl acetate. In either case,the organic layer or solution can be washed free of acid and inorganicsalts with Water, dried with sodium sulfate or other suitable agent andthe solvent then distilled in vacuo to leave theN-(3,3-dialkoxy-Z-ketopropyl) -N-(arylsulf0nyl) -p aminobenzoatecompound, generally as a yellowish sirupy residue.

In some instances, the product can be obtained in partially crystallineform upon allowing the oily product to stand. The crude product can,however, be used without further purification in July 31, 1948. They canbe prepared readily, as described in the co-pending application justmentioned, by reacting an arylsulfonyl halide with an alkyl ester ofp-aminobenzoic acid, of p-aminobenzoyl-glutamic acid, or of ap-aminobenzoyl-glutamyl-glutamic acid having up to 7 glutamic acidresidues in the molecule.

Dialkyl acetals of 1,2-oxidopropanol which can be used in the processinclude the dimethyl, diethyl, di-n-propyl, di-iso-propyl, dibutyl,diamyl and other dialkyl acetals. As a matter of convenience andavailability dialkyl acetals wherein the alkyl radicals each containless than 8 carbon atoms are preferred, although others can be used, ifdesired. It is apparent that the nature of the alkyl groups in the3,3-dialkyl-2- hydroxypropyl and in the 3,3-dialkyl-2-ketopropylradicals of the compounds (III) and (IV) are determined by theparticular 1,2-oxidopropanol diallzyl acetal used in the first step ofthe process.

Esters which can be used as starting com pounds in the process, with theproduction of the corresponding ester intermediates, include the methyl,ethyl, n-propyl, iso-propyl, butyl, amyl, hexyl, nonyl and other 'alkylesters. As a matter of convenience, lower alkyl esters containing lessthan about" 8 carbon atoms in the alkyl radicals are preferably used inthe process, although insofar as is knomrany alkyl ester can be used.

Although starting compounds containing substantially any arylsulfonylradical can be used in the process of the invention and in thepreparation of the corresponding arylsulfonyl intermediates and finalproducts, the preferred starting materials and intermediate products arethose containing the p-toluenesulfonyl radical due to the readyavailability of the p-toluenesulfonyl halides and to the generallycrystalline nature of the p-toluenesulfonyl' derivatives of compoundswith which the present invention is concerned. The invention is,however, not limited to compounds containing the p-toluenesulfonylradical and compounds containing other arylsulfonyl 5 ra'dieals, such asthe befiz'enesulfonyl, io-tolu'ene sulfonyl, maphthalenesul'fonyl,methylnaphthalenesulfonyl radicals and others, can be used, if desired.

-It should also he mnti'oiied that compounds containin a fiylsiilfohmmadman ha ving nen-hydroearbonsu-betituems ca'n he i'i's'e'd intheprocess iiffd the corresponding intermediate fi'nal roducts prepared,provided *only that the substituent is r-io'rr rea'tive u' nd'er therea'tion conditions. Such non-reactive substituents include chlorine,bromine, and the metnox yphenoxy, intro "and similar radicals. "It"should be mentioned further that, although the' present invention isconcerned primarily with compounds wherein "the sulfo'nyl radical is an'arylsulfonyl radical; the processjcan also-'be'carrietiout and thecorresponding *produets prepared using S'fialtifig materials 'containingallr-ylsulfonyl, aralkylsub fon'yl =orcy1oa1k ls i1fony1 "radicals, suchas the meth'anes'ulfonyl, 'ethane'siilfonyl, 'cyoloh'exylsiil fon'yl,and *pheriylm'ethanesulfonyl radicals.

The reaction or dialkyl "acetal bras-emopro'panm "with "an 1 'T-ary1su1fonyl) -*p-'aminohen- Zoateester can he "Carried 'out readily byheating thesnbstances'togethenm'referably with t'headdrti'on of acatalytic prop'or'tion of 'pyridi'ne'or" other tertiary amine.Approximately "equimol'ecnla'r proportions 'ofthe reactants canhe usedand the mixture preferably heated at from "about 100 degrees to about150 degrees Centigrade fio'r from abo'iitfi to QlbouflBOmimites. 'Th'eN-(3,3"dial k'oxy 2 -hydroxypropyl) N (aryl'snlfonyl)-paminobenz'o'at'eco'ni'pofih'diormed can' 'b'ei'solated fromthe reaction mixture, e. g.by Washingthe cru'ii'e reactionfpro duct thoroughly "with a suitablesolvent, such as naphtha o'r isopropanol, "toremove the catalys't andiifnrea'cted starting materials. 'Some of the N-i3l3-iiialkoxy2-hydroxypropyl) N ('arylsulfony-I) T-p-an'linobenz'oate esters are thusobtained as crystalline c'ompoiindshaving Well defined meltinghp'ointsand some as sirupy liquids. "They can "be 'hyiirolyzed to thecorresponding acids by mixing with aqueous alkalies or otherconventional alkalinehydro'lytio agents and acidifying -the aqueousr'eaction mixtureQpreferablY W itha mineral acid. Certain of theacids'are thus obtained 'as-s-oliilsubstances.

New compounds representedhy the. genericformnla (IV) whichcan'bevprepareii'by the methoii of the invention include arnongmanyothers, methyl N- (3,3-diethxy i 2 ketopropyll-litptoluenesul-fonyl)-p-aminobenzoate,iso=propyl N- 3,3-- di-n-hexoxy 2 ketopropyl) N'- (alphanaphthalenesulfony-l)-p-aminobenzoate, n-ootyl N (-33 --di-- n-octoxy--2 -'-ketopropy1) -N- tpethoxybenzenesulfonyl) p amino'benzoate,dimethyl N'- (N (3,3 -diethoxy-2-ketopropyl)N-(ptoluenesulfonylh-paminobenzoyl) rglutamatediiso-propyl N'- (N-(3,3-di-n-hexoxy 2 ketopropyl) N- (alpha riaphthalenesiilfonyl)'paminobenzoyl) -glutamate, di n-ootyl N( N'-'(3,3-di=nnonoxy "2ketopropyl) N'- (o 'chloro ipethoxybenzenesulfonyl) p :aminobenzoyl)glutamate, -"N-' (33 diethoxy ketopropyl) -'N- (ptoliienesulfonyl)epaminoben'zoic aci'd, :N 3,-3-din -:-hexoxy 2 letopropyl) N- (alpha--naph thaleries'ulfonyl) p-"aminobenzoic -aeid, N- 3,3-di=- T glutariiicacid.

'u'enesulfonyl) -'p-aminobenzoate "and two drops of pyridine washeatedifortwelve minutes'at 'degrees to degreesC. The *cl'e'a'r' meltwhichwals formedwas-cooled and-seeded with crystals of previouslyprepared ethyl N-(3j'3-diethoxy=2hydroxypro'pyl) -N (p toluenesulfonyl)-.paminobenzoate. The partially crystalline mass was triturated with-.amixture ef-six millilitersot petroleum naphtha and three milliliters ofisoprop'anol "and the mixture filtered. There was thus obtained "1.71grams of ethyl --N-(3;3-diethoX-y 2- hydroxyp'ropyly- Nl(p--'toluen'esulfonyl-) -ipaminobenzoate melting-at 89 degrees to 94degrees 0. Repeated. recrystallization of the product from'i-so'propanol--petrolenm naphtha raised the melting .point to 91degreesto 94'degrees C.

Following substantially the-same .procedure5h1it using anequi-molarproportion of the-:d-im'ethyl acetal of 2,3-oxidopropanal, thedi-n-propyl acetal of 2,3-oxidopropanaljtheiii-n-butyl acetal of 2,3-oxidopropanal, the di-isobutyl acetal of 2-,3- oiiiiiopropanal oror theiii-'iiodecyl 'act'a' l of '2',3- ozidopropanal in place of thediethyl'acetal of 2B-oxidopropahal, there are 'formed ethyl N-"(SBFdimethoxy 2 hydroxypropyl) "N (p tolu'en'esul'fon'yl'):p-aminohenzo'a'te, 'e'thyll N 't3'j3-die ne'prospoxy -2 hydroXyp'roWl)N "(,p lienesliliomil)ep aniinobenzoate, ethyl "N- ;3 'din-blitoxy -'2hydroxypropyl) N (p toluen'estilfon yl) -p-amin6benzoate, ethyl N-(3','3di-iso butoxy '2 -"h-y"droxypropyl) -"N '(p to1uen'esiilfonyl) epaminobenzoate, and ethyl 'N-(3,3-d.idodec-yloxy 2 --"hydroxypropyl) N.(p-"tol: uenesulfonyl)p-aminobenzoate, respectively. "Followingsii-bstaiitially'thesame proc'edurehrit using equi-molartproportions ofethyl Fri-"(benzenesvilfonyll =p-aniinobenzeate, n hexyl lT-(ot'o'lnenesulfohyl)-p-an'iinobenzoate, 'n-butylN(pchloroberiaenesulfonyll p aminobenzoate, 01' 6f n doii'eoylll Kb'etanaphthalenesulf-ohyl) 1oaminobenzoate'in filace of theethyl- N-lptoluenesulfonyl)-p-aminobenzoate, there are obtained ethyl N 3 ,3-'.'diethoxy- 2-hydroxyehropyl) N (ben- Empty-and nine tenthsigramsvoiN-i p-ltoluenesulfonylbp aniinobenzoyl chloride "and 23!.9 grams ofvdiethyl 11 eglutamate hydrochloride were dissolved in 300;millilitersof ethylene ilchloride and the solution cooled tobetween il degreesand'li) qlegrees C. The coldsolution wasstirred.vigorously:and22;3gramsoftriethylamine in 72 milliliters of:ethylene dichloride was added slowly over a period of about 20 minutes.The temperature of the mixture was held between 10 degrees and degreesC. during the addition of the triethylamine and the mixture then allowedto stand at room temperature for one hour. The mixture was then washedsuccessively with water, dilute hydrochloric acid, saturated aqueoussodium bicarbonate and finally with water. The colorless Solution thusobtained was dried with anhydrous sodium sulfate and naphtha was addeduntil the solution became opalescent. The mixture was then cooled tocause crystallization and filtered. The crystals, after drying,consisted of 36 grams. of diethyl N-(N-(p-toluene sulfonyl)-p-aminobenzoyl) -l-glutamate melting at 124 degrees to 126 degrees C.

Example 3.Diethyl N -(N -(3,3-d2'ethoxy-2-hy dmzcypropyl)-N-(p-toluenesulfonyl) -p-aminobenzoyl) -1 glutamate One and six-tenthsgrams of the diethylacetal of 2,3-oxidopropanal and five drops ofpyridine were added to 4.77 grams of fused diethyl N'-(N- (p"-'toluenesulfonyl) p aminobenzoyl) 1- glutamate at degrees C. The mixturewas stirred for about 30 minutes at degrees to degrees C. The highlycolored mass consisted chiefly of diethyl N'-(N-(3,3-diethoxy-2-hydroxypropyl) N (p toluenesulfonyl) paminobenzoyD-l-glutamate. It had an index of refraction without furtherpurification of Following substantially the same procedure, but using anequi-molar proportion of the dimethyl acetal of 2,3-oxidopropanal, thedi-n-propyl acetal of 2,3-oxidopropanal, the di-n-butyl acetal of2,3-oxidopropanal, the di-iso-butyl acetal oi 2,3-oxidopropanal or thedi-dodecyl acetal of 2,3- oxidopropanal in place of the diethyl acetalof 2,3-oxidopropanal, there are obtained diethyl N (N (3,3 dimethoxy 2hydroxypropyl) N- (p toluenesulfonyl) p aminobenzoyl) lglutamate,diethyl N (N- (3,3-di-n-propoxy-2- hydroxypropyl) N (p toluenesulionyl)paminobenzoyl) -l-g1utamate, diethyl N'-(N-(3,3- di n butoxy 2hydroxypropyl) N .(ptoluenesulfonyl) p aminobenzoyl) 1 glutamate,,diethyl N '-(N-(3,3-di-iso-butoxy-2-hydroxypropyl) N (ptoluenesulfonyl) paminobenzoyl)-l-glutamate, and diethyl N-(N- (3,3 didodecyloxy 2 hydroxypro'pyD-N- (p toluenesulfonyl) p aminobenzoyl) 1-glutamate, respectively.

Following substantially the same procedure, but using an equi-molarproportion of diethyl N '-(N- (benzenesulfonyl) p aminobenzoyl) lglutamate, di-n-hexyl N'- (N-(o-toluenesulfonyl)-paminobenzoyl)-1-glutamate, di-n-butyl N-(N- (p chlorobenzenesulfonyl)p aminobenzoyl) I-glutamate, or of di-n-dodecylN'-(N-(betanaphthalenesulfonyl) p aminobenzoyl) 1- glutamate in place ofdiethyl N '-(N-(p-toluenesulfonyl) p aminobenzoyl) 1 glutamate, thereare obtained diethyl N'-(N-(3,3-diethoxy 2 hydroxypropyl) N(benzenesulfonyl) paminobenzoyl)-l-glutamate, di-n-hexyl N'-(N- (3,3diethoxy 2 hydroxypropyl) N (otoluenesulfonyl) p aminobenzoyl) 1glutamate, di-n-butyl N (N- (3,3-diethoxy-2-hydroxypropyl) N (pchlorotoluenesulfonyD- p-aminobenzoyl)-1-glutamate and di-n-dodecyl N (N(3,3 diethoxy 2 hydroxypropyD- N (beta naphthalenesulfonyl) paminobenzoyl) -1-g1utamate, respectively.

8 Example 4.-N-(3,3-dietho:cy-2-hydroxypropyl) N (p-toluenesulfonyl)-p-aminobenzoic acid A quantity of ethyl N-(3,3-diethoxy-2hydroxypropyl)N (p-toluenesulfonyl) -p-aminobenzoate is warmed for several minuteswith slightly more than one molar portion of dilute aqueous or alcoholicsodium hydroxide and the mixture then cooled, diluted, acidified andfiltered. There is thus obtained N-(3,3-diethoxy- 2 hydroxypropyl) N (ptoluenesulfonyl) -paminobenzoic acid.

- Following substantially the same procedure ethyl N- 3,3-dimethoxy-2hydroxypropyl) -N- ptoluenesulfonyl) -p-aminobenzoate, ethyl N-(3,3- din propoxy-2-hydroxypropyl) -N-(p-toluenesulfonyl)-p-aminobenzoate, ethylN-(3,3-di-nbutoxy-2 -hydroxypropyl) -N (p-toluenesulfonyl)p-aminobenzoate, ethyl N-(3,3-di-isobutoxy-2- hydroxypropyl)-N-(p-toluenesulfonyl) -p-aminobenzoate, butylN-(3,3-di-dodecyloxy-2-hydroxypropyl) -N- (p-toluenesulfonyl)-p-amin0benzoate, n hexyl N (3,3-diethoxy-2-hydroxypropy1) -N-(o-toluenesulionyl)-p-aminobenzoate, n-dodecyl N (3,3 diethoxy 2hydroxypropyl) -N-(betanaphthalenesulfonyl)-p-aminobenzoate, diethyl N'(N (3,3 diethoxy-2-hydroxypropyl) -N-(ptoluenesulfonyl) p-aminobenzoyl)-l-glutamate, di n butyl N'-(N-(3,3-diethoxy-2hydroxypropyl) N-(p-ch1orobenzenesulfonyl) -p-aminobenzoyl) -l-glutamate, diethylN-(N-(3,3-diethoxy- 2 hydroxypropyl) N-(benzenesulfonyl)-p-aminobenzoyD-l-glutamate and di-dodecyl N'-(N- 3,3 diethoxyZ-hydroxypropyl) -N-(beta-naphthalenesulfonyl) p-aminobenzoyl)-l-glutamate are hydrolyzed to form N-(3,3-dimethoxy-2-hydroxypropyl) N(p-toluenesulfonyl) -p-aminobenzoic acid, N-(3,3-di-n-propoxy-2-hydroxypropyl) N (p-toluenesulfonyl) -p-aminobenzoicacid, N (3,3 di-n-butoxy-2-hydroxypropyl) -N- (p-toluenesulfonyl)-p-aminobenzoic acid, N- (3,3- di iso butoxy-2-hydroxypropyl) -N-(p-toluenesulfonyl) p aminobenzoic acid, N-(3,3-di-dodecyloxy 2hydroxypropyl) N-(p-toluenesulfonyD-p-aminobenzoic acid,N-(3,3-diethoxy-2- hydroxypropyl) -N- (o-toluenesulfonyl)-p-aminobenzoic acid, N-(3,3-diethoxy-Z-hydroxypropyl) N betanaphthalenesulfonyl) -p-aminobenzoic acid, N(N-(3,3-diethoxy-2-hydroxypropyl) -N- (p-toluenesulfonyl)-p-aminobenzoyl) -l-glutamic acid, N (N -(3,3-diethoxy-2-hydroxypropyl)-N- (p chlorobenzenesulfonyl) -p-aminobenzoyl) -1- glutamic acid, N (N-(3,3-diethoxy-2-hydroxypropyl) N-(benzenesulfonyl) -p-aminobenzoyl)l-glutamic acid, and N'-(N-(3,3-diethoxy-2-hydroxypropyl) N-(beta-naphthalenesulfonyl) -p-' aminobenzoyl)-1glutamic acid,respectively.

Example 5.-Ethyl N-(3,3-diethoxy-2-ketopropyl) -N- (p-toluenesulfonyl)-paminobenzoate Approximately 3.2 grams of ethyl N- (p-toluenesulfonyl)-p-aminobenzoate was reacted with the diethyl acetal of2,3-oxidopropanal by the method described in Example 1. The crudereaction mixture prior to seeding was dissolved in 10 milliliters ofglacial acetic acid and the solution mixed with a solution of one gramof chromic anhydride in 20 milliliters of glacial acetic acid. Themixture was allowed to stand at room temperature for about three hoursand the acetic acid distilled in vacuo. The residue was triturated withether and the mixture filtered; The ethereal filtrate was washed withwater, dried and the ether volatilized. The residue consisted of ethylN-(3,3- diethoxy 2 -ketopropyl) -N- (p-toluenesulfonyl) 11 12N-(p-toluenesulfonyl) -p-aminobenzoyl) 1 glu- 7. Diethyl N '-(N-(3,3-diethoxy-2-ketopropyl) tamic acid, N-(N-(3,3-diethoxy-2-ketopropy1)-N-(p-toluenesulfonyl) -p-aminobenzoyl) gluta- N- (pchlorobenzenesulfonyl) -p-aminobenzoyl) mate. l-glutamic acid,N'-(N-(3,3-diethoxy-2-ketopro- 8. The method which includes: oxidizingan pyl) N (benzenesulfonyl) -p-am.inobenzoyl) -1- 5 hydroxy acetalhaving the formula (alkyl-O-MCH-UHOH-CHP-NGC0(NH47HCH2CH2COLOR' aryl-SO:

glutamic acid, and N'-(N-(3,3-diethoxy-2-ketowherein R i a member of thegroup consisting 'propyl)-N-(beta-naphthalenesulfonyl)-p-aminoofhydrogen and the alkyl radicals and n is a -benzoyl) -1-glutamic acid,respectively. member of the group consisting of zero and the The ketoesters thus obtained are hydrolyzed by positive integer 1 to form a ketoacetal having dilute alkali to form the corresponding keto acids. theformula 000R (alkyl-O-hCH-C o-cm-N comm ncmomcohon' aryl- O: I

It is to be understood that the invention is not 9. The method of claim8 wherein n is zero and to be limited to the exact details of operationor R is an alkyl radical. exact compounds shown and described, as ob-10. The method of claim 8 wherein n is the vious modifications andequivalents will be apparpositive integer 1 and R is an alkyl radical.ent to one killed in the art, and the invention is, 11. The method ofclaim 8 wherein the alkyl therefore, to be limited only by the scope ofthe radicals each contains less than 8 carbon atoms. appended claims.12. The method of claim 8 wherein the arylsul- We claim: fonyl radicalis the p-toluenesulfonyl radical. 1. A compound having the formula 13.The method of claim 8 wherein the hydroxy 000R (alkyl-O-JzCH-C o-cm-N oomncncmomo O).OR'

aryl-SO:

wherein R is a member of the group consisting acetal is ethyl N (3,3diethoxy 2 --hydroxyof hydrogen and the alkyl radicals and n is apropyl) N (p toluenesulfonyl) p aminomember of the group consisting ofzero and the benzoate.

positive integer l. 14. The method of claim 8 wherein the hydroxy 2. Acompound as claimed in claim 1 wherein acetal is diethylN-(N-(3,3-diethoxy-2-hydroxythe alkyl radicals each contains less than 8carpropyl) N (p toluenesulfonyl) p aminobon atoms. benzoyl) -glutamate.

3. A compound as claimed in claim 1 wherein 15. The method whichincludes: oxidizing an R is an alkyl radical and n is zero. '4 hydroxyacetal ester having the formula GOO-alkyl (alkyl-0);CHCHOH-CH:N ooNHcHoH=omc0),.-0-a1r 1 aryl- O:

' 4. A compound as claimed in claim 1 wherein wherein n is a member ofthe group consisting of R is an alkyl radical and n is the positiveinzero and the positive integer l to form a keto teger 1. acetal etserhaving the formula 5. A compound as claimed in claim 1 wherein andhydrolyzing the keto acetal ester with an the arylsulionyl radical isthe p-toluenesulfonyl alkali to form a keto acetal acid having theforradical. mula coon (alkylO-)z cH-o O-CHr-N c owner-romaine 0),.011

aryl 01 6. Ethy] N-(3,3-diethoxy-2-ketopropyl)-N-(p- DAVID) I. WEISBLAT.toluenesulfonyl)-p-aminobenzoate. BARNEY J. MAGERLEIN.

No references cited.

1. A COMPOUND HAVING THE FORMULA
 15. THE METHOD WHICH INCLUDES:OXIDIZING AN HYDROXY ACETAL ESTER HAVING THE FORMULA